Cytochrome b-c1 complex subunit Rieske, mitochondrial

UQCRFS1 encodes the Rieske iron-sulfur protein, a catalytic core subunit of the cytochrome b-c1 complex (complex III) embedded in the inner mitochondrial membrane (UniProt: P47985). It contains a [2Fe-2S] iron-sulfur cluster essential for electron transfer during oxidative phosphorylation, cycling between conformational states to shuttle electrons from ubiquinol to cytochrome c as part of the Q cycle that generates the proton gradient driving ATP synthesis.

Complex III is a critical component of the mitochondrial electron transport chain, and UQCRFS1 incorporation represents a penultimate assembly step (UniProt: P47985). Pathogenic variants cause mitochondrial complex III deficiency (MIM 618775), a recessive disorder presenting with fetal bradycardia, hypotonia, cardiomyopathy, and lactic acidosis due to impaired oxidative metabolism.

In Alzheimer's disease, UQCRFS1 shows ambiguous regulation across subcellular fractions in post-mortem brain tissue (Chaparral AD proteomics), with a mean log2 fold-change of 0.08 relative to age-matched controls. This minimal average change suggests either stable expression overall or differential regulation by cellular compartment, consistent with complex III's fundamental housekeeping role in neuronal energy metabolism.